Nasal delivery devices

ABSTRACT

A nasal delivery device for and method of delivering particulate substance to the nasal airway of a subject, the delivery device comprising: a body assembly including a mouthpiece unit which includes a mouthpiece through which the subject in use exhales, and a substance-supply unit which is fluidly connected to the mouthpiece unit and actuatable to provide particulate substance for delivery to the nasal airway of the subject; wherein the body assembly is configured to receive a replaceable nosepiece unit which includes a nosepiece and contains a container containing particulate substance.

The present invention relates to a nasal delivery device for and methodof delivering particulate substance, in particular a powdered substance,to the nasal airway of a subject, and a container for use with the same.

There is an increasing interest in the nasal delivery of substances,typically pharmaceutical drugs, both as powders and liquids, for topicaland systemic delivery.

Current delivery systems are not suited to the delivery of substances tothe upper posterior region of the nasal airway, in particular targeteddelivery to the olfactory region and the sinus ostia.

U.S. Pat. Nos. 4,013,075 and 4,889,114 disclose examples of prior artinhalation devices, which provide for the inhalation of a powderedsubstance from a capsule.

WO-A-00/051672, the content of which is herein incorporated byreference, discloses a delivery device for delivering a substance, inparticular a medicament, in a bi-directional flow through the nasalcavities, that is, an air flow which passes into one nostril, around theposterior margin of the nasal septum and in the opposite direction outof the other nostril. A particular feature of this bi-directional modeof delivery is the ability to target defined regions in the nasalairway, for both topical and systemic delivery, in particular the upperposterior region which cannot be targeted with existing systems.

The present inventors have recognized that the delivery of powderedsubstances using the exhalation breath of a subject still presents asignificant challenge.

It is an aim of the present invention to provide a delivery device whichallows for delivery of powdered substances from containers, typicallycapsules or blisters, which contain a pre-metered dose of substance withthe appropriate particle size distribution and surface properties, whereusing the exhalation breath of the subject.

In one aspect the present invention provides a nasal delivery device fordelivering particulate substance to the nasal airway of a subject, thedelivery device comprising: a body assembly including a mouthpiece unitwhich includes a mouthpiece through which the subject in use exhales,and a substance-supply unit which is fluidly connected to the mouthpieceunit and configured to receive a replaceable nosepiece unit whichincludes a nosepiece and contains a container containing particulatesubstance, wherein the substance-supply unit is actuatable to provideparticulate substance for delivery to the nasal airway of the subject.

In one embodiment the delivery device further comprises: a replaceablenosepiece unit which includes a nosepiece for fitting to a nostril of asubject, and a container chamber which contains a container containingparticulate substance.

In one embodiment the delivery device is configured to prevent operationuntil a nosepiece unit is fitted to the body assembly.

In one embodiment the body assembly includes an actuation mechanismwhich is manually actuatable by the subject to open the container, andthe delivery device is configured to prevent actuation of the actuationmechanism until the nosepiece unit is fitted to the body assembly.

In one embodiment the substance-supply unit includes an interlockmechanism which adopts a first, locking configuration when a nosepieceunit is not fitted to the body assembly, in which the actuationmechanism is not actuatable, and a second, released configuration when anosepiece unit is fitted to the body assembly, in which the actuationmechanism is actuatable.

In one embodiment the interlock mechanism comprises an interlock memberwhich is movably disposed between locking and released positions andnormally biased to the locking position.

In one embodiment the substance-supply unit includes a valve unit whichis operable between a first, closed configuration in which a fluidcommunication path with the mouthpiece is closed, and a second, openconfiguration in which the fluid communication path is open.

In one embodiment the interlock mechanism is configured to lock thevalve unit in the closed configuration when the interlock mechanism isin the locking configuration and allow operation of the valve unit whenthe interlock mechanism is in the released configuration.

In one embodiment the valve unit includes a locking element which isengaged by the interlock mechanism when the interlock mechanism is inthe locking configuration to prevent operation of the valve unit.

In another aspect the present invention provides a nasal delivery devicefor delivering particulate substance to the nasal airway of a subject,the delivery device comprising: a mouthpiece unit which includes amouthpiece through which the subject in use exhales; a nosepiece unitwhich includes a nosepiece for fitting to a nostril of the subject; anda substance-supply unit which is configured to receive a containercontaining particulate substance and operable to provide a meteredamount of substance in fluid communication with the mouthpiece andnosepiece units, such that an exhalation air flow delivered through thesubstance-supply unit entrains the substance.

In one embodiment the container comprises first and second parts whichtogether define an enclosed chamber and are movable between a first,closed configuration in which the container is closed and a second, openconfiguration in which the container is open, and the substance-supplyunit is operable to move the first and second parts of the container tothe open configuration.

In one embodiment the first and second parts of the container areslideably disposed relative to one another and each include at least oneaperture; which are closed with the first and second parts in the closedconfiguration and opened by sliding of the first and second parts to theopen configuration.

In one embodiment the substance-supply unit comprises a support member,and a body section which is movable relative to the support memberbetween a first, container-receiving position for receiving a containerin the closed configuration, and a second, operative position in whichthe container is opened and disposed in fluid communication with themouthpiece and nosepiece units.

In one embodiment the body section is rotatably disposed to the supportmember.

In one embodiment the body section includes a container-receivingaperture, which allows for introduction of a container thereinto whenthe body section is in the container-receiving position and is closedwhen the body section is in the operative position.

In one embodiment one of the support member and the body sectionincludes an inlet aperture which is fluidly isolated from the mouthpieceunit when the body section is in the container-receiving position andfluidly connected to the mouthpiece unit when the body section is in theoperative position.

In one embodiment the support member and the body section each includean engagement feature for engaging respective ones of the first andsecond parts of the container, and the support member and the bodysection are axially movable relative to one another, such that, onmovement of the body section from the container-receiving position tothe operative position, the first and second parts of the container aremoved to the open-configuration.

In one-embodiment the support member and the body section are coupled bya cam mechanism, which provides that the engagement features thereof aremoved between a first spacing in which the container is receivedtherebetween, a second, closer spacing in which the first and secondparts of the container are moved to the open configuration, and a thirdspacing in which the container is moveable axially between theengagement features.

In one embodiment the delivery device further comprises: a housing whichsupports the mouthpiece unit, the nosepiece unit and thesubstance-supply unit.

In one embodiment the substance-supply unit includes acontainer-receiving member which is movably disposed to the housingbetween an open position for enabling loading of a container thereinto,and a closed position in which the container is contained within thehousing.

In one embodiment the container-receiving member includes a cavity whichdefines an air flow channel between the mouthpiece and nosepiece units,such that an air flow is delivered therethrough on exhalation by thesubject through the mouthpiece, and a support section for supporting thecontainer in the cavity.

In one embodiment the container comprises a main body part and first andsecond bearing support parts at the respective ends of the body part,and the support section includes first and second container supports forrotatably supporting the respective support parts of the container.

In one embodiment the support parts of the container comprisepart-spherical projections and the container supports comprisepart-spherical recesses.

In one embodiment the substance-supply unit includes a locking mechanismfor locking the container-receiving member in the closed position.

In a further aspect the present invention provides a nasal deliverydevice for delivering particulate substance to the nasal airway of asubject, the delivery device comprising: a body assembly including amouthpiece unit which includes a mouthpiece through which the subject inuse exhales, and a substance-supply unit which is fluidly connected tothe mouthpiece unit and actuatable to provide particulate substance fordelivery to the nasal airway of the subject; wherein the body assemblyis configured to receive a replaceable nosepiece unit which includes anosepiece and contains a container containing particulate substance.

In one embodiment the delivery device further comprises: a replaceablenosepiece unit which includes a nosepiece for fitting to a nostril of asubject, and a container chamber which contains a container containingparticulate substance.

In one embodiment the delivery device is configured to prevent operationuntil a nosepiece unit is fitted to the body assembly.

In one embodiment the body assembly includes an actuation mechanismwhich is manually actuatable by the subject to open the container, andthe delivery device is configured to prevent actuation of the actuationmechanism until the nosepiece unit is fitted to the body assembly.

In one embodiment the actuation mechanism is locked in a lockedconfiguration when a nosepiece unit is not fitted to the body assembly,such as to prevent operation of the actuation mechanism.

In one embodiment the nosepiece unit includes a release member forreleasing the actuation mechanism from the locked configuration onfitting the nosepiece unit to the body assembly.

In one embodiment the actuation mechanism includes an actuation memberwhich is latched in a locked position in the locked configuration of theactuation mechanism, and the release member of the nosepiece unit isoperative to release the latched actuation member on fitting thenosepiece unit to the body assembly.

In one embodiment the nosepiece unit is fitted to the body assembly inone, fitting sense and removed from the body assembly in the opposite,removal sense, and the release member includes a support element, anengagement element for engaging the actuation mechanism and a frangibleconnection element which connects the support element to the engagementelement, wherein the engagement element presents a substantially rigidstructure when the nosepiece unit is fitted in a first instance to thebody assembly and is operative to release the actuation mechanism fromthe locked configuration, and is deformed on removing the nosepiece unitfrom the body assembly.

In one embodiment the body assembly further comprises a lockingmechanism for locking the actuation mechanism from further operationfollowing a predeterminable number of operations of the actuationmechanism.

In one embodiment the locking mechanism comprises a rotatable elementwhich is indexed with each actuation of the actuation mechanism andlocks the actuation mechanism to prevent further operation thereoffollowing a predeterminable number of operations of the actuationmechanism.

In a yet further aspect the present invention provides a containercomprising first and second body parts which together define an enclosedchamber and are movable between a first, closed configuration in whichthe container is closed and a second, open configuration in which thecontainer is open.

In one embodiment the first and second body parts are slideably disposedrelative to one another and each include at least one aperture, whichare closed with the first and second body parts in the closedconfiguration and opened by sliding of the first and second body partsto the open configuration.

In one embodiment the first and second body parts include inter-engagingguides which provide for axial sliding of the first and second bodyparts without substantially any rotation thereof.

In one embodiment the container is an elongate container.

In one embodiment the container is a capsule.

In one embodiment the container is for containing particulate substance.

In a still further aspect the present invention provides a containercomprising a main body part and first and second bearing support partsat the respective ends of the main body part which provide bearingsupports about which the container is rotatable.

In one embodiment the support parts-comprise part-spherical projections,and preferably substantially hemi-spherical projections.

In one embodiment the container is an elongate container.

In one embodiment the container is a capsule.

In one embodiment the container is for containing particulate substance.

Preferred embodiments of the present invention will now be describedhereinbelow by way of example only with reference to the accompanyingdrawings, in which:

FIG. 1 illustrates a side view of a delivery device in accordance with afirst embodiment of the present invention;

FIG. 2 illustrates a plan view of the delivery device of FIG. 1;

FIG. 3 illustrates a fragmentary perspective view of the delivery deviceof FIG. 1, prior to fitting of the nosepiece unit to the body assembly;

FIG. 4 illustrates the perspective view of FIG. 3, where part cut-away;

FIG. 5 illustrates a perspective view of the delivery device of FIG. 1,with the nosepiece unit fitted to the body assembly;

FIG. 6 illustrates a part cut-away fragmentary perspective view of thedelivery device of FIG. 1 following exhalation by the subject throughthe mouthpiece;

FIG. 7 illustrates a perspective view of a delivery device in accordancewith a second embodiment of the present invention;

FIG. 8 illustrates a part cut-away perspective view from the rear andone side of the delivery device of FIG. 7, with the cover in an openposition;

FIG. 9 illustrates a part cut-away perspective view from the front andone side of the delivery device of FIG. 7, with the cover in an openposition;

FIG. 10 illustrates a part cut-away perspective view from the rear andone side of the delivery device of FIG. 7, with the container chamber inthe open position;

FIG. 11 illustrates a part cut-away perspective view from the rear andone side of the delivery device of FIG. 7, with the container chamber inthe intermediate position;

FIG. 12 illustrates a container in accordance with one embodiment of thepresent invention, in the closed configuration;

FIG. 13 illustrates the container of FIG. 12 in the open configuration;

FIG. 14 illustrates a perspective view of a delivery device inaccordance with a third embodiment of the present invention, with thesubstance-supply unit in the open position for receiving a container;

FIG. 15 illustrates the perspective view of FIG. 14, where partiallycut-away and with the substance-supply unit loaded with a container;

FIG. 16 illustrates a perspective view of the delivery device of FIG.14, where partially cut-away and with the substance-supply unit loadedwith a container;

FIG. 17 illustrates a perspective view of the delivery device of FIG.14, where partially cut-away and with the substance-supply unit loadedwith a container and the actuating member of the rupturing mechanism inthe depressed position;

FIG. 18 illustrates a part cut-away perspective view of a deliverydevice in accordance with a fourth embodiment of the present invention;

FIG. 19 illustrates a perspective view of the nosepiece unit of thedelivery device of FIG. 18;

FIG. 20 illustrates a part cut-away fragmentary perspective view of thedelivery device of FIG. 18, where the nosepiece unit is being removedfrom the body assembly and the release member of the nosepiece unit isbeing deformed by engagement with the latch element of the actuatingmember of the rupturing mechanism;

FIG. 21 illustrates the perspective view of FIG. 20 in enlarged scale;and

FIGS. 22 to 26 illustrate vertical sectional views of the operativesequence of the delivery device of FIG. 18.

FIGS. 1 to 6 illustrate a delivery device in accordance with a firstembodiment of the present invention.

The delivery device comprises a main, body assembly 3 and a nosepieceunit 5, which contains a container C containing substance to bedelivered to the nasal cavity of a subject and is removably fitted tothe body assembly 3, such as to allow for re-use of the body assembly 3,as will be described in more detail hereinbelow.

In this embodiment the container C comprises a capsule, but could haveany form which contains a metered dose of substance, such as a blister.

The body assembly 3 comprises a housing 7, a mouthpiece unit 9 and asubstance-supply unit 11 which is fluidly connected to the mouthpieceunit 9 and to which the nosepiece unit 5 is fitted.

The mouthpiece unit 9 comprises a mouthpiece 15 which in use is grippedin the lips of a subject, and an air flow channel 17 which is fluidlyconnected to the substance-supply unit 11.

In this embodiment the housing 7 and the mouthpiece unit 9 areintegrally formed, typically from a plastics material.

The substance-supply unit 11 comprises a body section 21 which receivesthe nosepiece unit 5, a rupturing mechanism 23 which is operable torupture the container C as contained by the nosepiece unit 5, and aninterlock member 25 which is operative to prevent operation of therupturing mechanism 23 without the nosepiece unit 5 being fitted, or atleast being fitted properly, to the body section 21.

The body section 21 comprises a body member 29 which includes a cavity31, in this embodiment cylindrical in shape, an inlet 33 which is influid communication with the cavity 31 and fluidly connected to the airflow channel 17 of the mouthpiece unit 9, and an outlet 35 which is influid communication with the cavity 31 and fluidly connected to thenosepiece unit 5 when fitted to the body section 21. With thisconfiguration, an exhalation air flow, as delivered through themouthpiece unit 9, is delivered through the cavity 31 of the bodysection 21 and from the nosepiece unit 5.

The body section 21 further comprises a first guide 41, in thisembodiment comprising a pair of laterally-extending slots 43 on opposedsides of the body member 29, which act to guide the rupturing mechanism23 laterally to the body member 29 in rupturing the contained containerC.

The body section 21 further comprises a second guide 45, in thisembodiment comprising a first pair of longitudinally-extending slots 47on opposed sides of the body member 29, which act to guide the interlockmember 25 longitudinally to the body member 29, and a thirdlongitudinally-extending slot 49, which slideably contains a contactelement 87 of the interlock member 25 and receives a contact element 97on the nosepiece unit 5 in providing for release of the interlock member25, as will be described in more detail hereinbelow.

The substance-supply unit 11 further comprises a valve 51 which isdisposed at the inlet 33 of the body member 29 and operable between afirst, closed position, as illustrated in FIG. 4, which substantiallyprevents an air flow through the cavity 31 of the body member 29, and asecond, open position, as illustrated in FIG. 6, which allows for a flowthrough the cavity 31 of the body member 29.

In this embodiment the valve 51 is a pressure-sensitive valve which issuch as to prevent an air flow through the cavity 31 until apredetermined pressure has been developed upstream thereof.

In this embodiment the valve 51 comprises a flap member 57 which ishingeable about a pivot 59 and normally biased to a closed, sealingposition by a resilient element 61, here a spring, such that apredetermined pressure is required to overcome the biasing force of theresilient element 61.

In this embodiment the flap member 57 includes a locking element 63,here in the form of an arm, which is operably coupled to the interlockmember 25, such that the flap member 57 is locked in the closed positionwhen the nosepiece unit 5 is not fitted to the substance-supply unit 11and is free to be moved to the open position when the nosepiece unit 5is fitted to the substance-supply unit 11, as will be described in moredetail hereinbelow.

In this embodiment the rupturing mechanism 23 comprises' an actuatingmember 73, here in the form of a button, which is configured to bedepressed by the subject, a piercing element 75, here including twopins, which is supported by the actuating member 73 and operable topierce the container C, and thereby provide for release of the containedpowdered substance on the generation of a flow through the cavity 31 ofthe body section 21, and a biasing element 76, here a resilient element,such as a compression spring, for biasing the actuating member 73 to aninoperative position.

The actuating member 73 includes at least one guide element 77, here apair of guide elements 77 in the form of arms, which are slideablydisposed in the slots 43 of the first guide 41 of the body section 21.In this embodiment the at least one guide element 77 includes a detent79, which retains the actuating member 73 captive in the first guide 41.

The interlock mechanism 25′comprises an interlock member 81 which isslideably disposed to the body section 21, in this embodimentlongitudinally along the length thereof, and a biasing element 83, herea resilient element, such as a compression spring, for normally biasingthe interlock member 81 to a locking position, as illustrated in FIG. 3,such as to prevent operation of the actuation mechanism 23 when thenosepiece unit 5 is not fitted to the substance-supply unit 11.

In this embodiment the interlock member 81 comprises at least one guideelement 85, here a pair of guide elements 85 in the form of arms, whichare slideably disposed in the slots 47 of the second guide 45 of thebody section 21, a contact element 87, here an elongate element, whichis slideably disposed in the slot 49 of the second guide 45 of the bodysection 21, and a locking element 89, here defined by an aperture, whichis operative to engage with the locking element 63 on the flap member57.

With this configuration, the interlock member 81, when biased to thelocking position, as illustrated in FIG. 3, acts to lock the flap member57 in the closed position by engagement of the locking element 89 of theinterlock member 81 and the locking element 63 of the flap member 57,and the guide elements 85 of the interlock member 81 are located such asto prevent movement of the guide elements 77 of the actuating member 73,and thereby prevent actuation of the same, and, when the nosepiece unit5 is fitted to the substance-supply unit 11, as will be described inmore detail hereinbelow, the interlock member 81 is moved against thebias of the biasing element 83 to a released position, in which thelocking element 89 of the interlock member 81 is disengaged from thelocking element 63 of the flap member 57, such as to allow for the flapmember 57 to be moved and opened on exhalation by the subject throughthe mouthpiece unit 9 at a predetermined flow rate, and the guideelements 85 of the interlock member 81 are moved clear of the guideelements 77 of the actuating member 73, such as to allow for actuationof the actuating member 73.

In one embodiment the mouthpiece unit 9 could include a heat exchangerwhich is in fluid communication with the mouthpiece 15 and acts to drawheat from the exhaled air flow as delivered through the mouthpiece 15,thus decreasing the temperature of the air flow as delivered to thecavity 31. By decreasing the temperature of the air flow, the humidityof the air flow is reduced, with the water vapor condensing in the heatexchanger, and the impact of condensation is significantly reduced, thusallowing for successive doses of powdered substance to be deliveredwithout affecting the release of powdered substance from the containersC.

The nosepiece unit 5 comprises a nosepiece 91, in this embodiment afrusto-conical section, which is inserted into a nostril of the subject,in this embodiment to provide a sealing fit therewith, and a containerchamber 93 which is in fluid communication with the nosepiece 91 andcontains a container C containing a powdered substance for delivery tothe nasal cavity of the subject.

In this embodiment the nosepiece unit 5 further comprises a grid, here agauze, which is disposed between the nosepiece 91 and the containerchamber 93, such as to prevent the container C or any parts thereof,such as resulting from rupturing of the container C, from passingthrough the nosepiece 91 and entering the nasal cavity of the subject.

In this embodiment the container chamber 93 and the grid, as componentswhich contact the container C and the contained powder, are fabricatedfrom a material having a low moisture sensitivity, here a plasticsmaterial, such as to reduce any tendency to become tacky in the presenceof moisture, and therefore reduce the tendency for the container C andthe powdered substance as contained thereby to adhere to the wall of thecontainer chamber 93 or the grid.

In this embodiment the nosepiece 91, as a component which contacts thepowdered substance, is fabricated from a material having a low moisturesensitivity, here a plastics material, such as to reduce any tendency tobecome tacky in the presence of moisture, and therefore reduce thetendency for the powdered substance to adhere to the wall of thenosepiece 91.

In one embodiment the container C is a gelatine capsule;

In another embodiment the container C can be manufactured from amaterial which has a reduced tendency to become tacky in the presence ofmoisture, as occurs with gelatine capsules, and therefore reduce thetendency for the container C to adhere to the wall of the containerchamber 93 or the grid.

In one embodiment the container C is formed of a cellulose derivative,such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose,methylcellulose, ethylcellulose and carboxymethylcellulose

In another embodiment the container C can comprise a plastics material,preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweightmaterial, such as thin-wall section polymeric materials, which reducesthe energy required to move the container C, typically by one or both ofvibration and rotation, and thereby allow the delivery device to beoperated at reduced flow rates, which is particularly advantageous fornasal delivery.

In an alternative embodiment the container C can include an outercoating of a material, such as parylene, which has a reduced tendency tobecome tacky in the presence of moisture, as occurs with gelatinecapsules, and therefore reduce the tendency for the container C toadhere to the wall of the container chamber 93 or the grid.

In this embodiment, the container C is cylindrical in shape withhemispherical ends.

In other embodiments the container C could have other geometric forms,such as spherical, which allows for efficient powder release at low flowrates.

The nosepiece unit 5 further comprises a contact element 97, in thisembodiment an axially-extending element, which is configured to be asliding fit in the third slot 49 of the second guide 45 of the bodysection 21 of the substance-supply unit 11, such that, on inserting thenosepiece unit 5 into the body section 21, the contact element 97engages the contact element 87 of the interlock member 81, in thisembodiment the distal end thereof, such as to move the interlock member81 to the released position.

Operation of the delivery device will now be described hereinbelow.

A subject first inserts a nosepiece unit 5 into the body section 21 ofthe substance-supply unit 11. On inserting the nosepiece unit 5 into thebody section 21, the contact element 97 thereof engages the contactelement 87 of the interlock member 81, such as to move the interlockmember 81 to the released position when the nosepiece unit 5 is fullyinserted into the substance-supply unit 11. With the interlock member 81in the released position, the flap member 57 is disengaged from thelocking element 89 of the interlock member 81 and free to be moved by anexhalation air flow, and the actuating member 73 of the rupturingmechanism 23 is operable by the subject.

The subject then operates the rupturing mechanism 23 to rupture thecontainer C as contained in the container chamber 93 of the nosepieceunit 5.

The subject then inserts the nosepiece 91 into one of his/her nostrils,grips the mouthpiece 15 in his/her mouth, and exhales through themouthpiece 15.

The exhaled air flow, where having a sufficient flow rate, is thendriven through the cavity 31 of the body section 21 and the containerchamber 93, which acts to move the container C, in this embodiment byvibration and rotation, and entrain the powdered substance as containedby the container C.

The exhaled air flow, as then entraining the powdered substance, isdelivered though the nosepiece 91 into one nasal cavity of the subject.

In this embodiment the exhaled air flow is such as to pass around theposterior region of the nasal septum, and into the other nasal cavity,thereby achieving a bi-directional air flow as described in theapplicants' earlier WO-A-00/051672.

Following use, the nosepiece unit 5 is then removed and theabove-described procedure can be repeated with another nosepiece unit 5.

FIGS. 7 to 13 illustrate a delivery device in accordance with a secondembodiment of the present invention.

The delivery device comprises a housing 103, a nosepiece unit 105, amouthpiece unit 109 and a substance-supply unit 111 which is fluidlyconnected to the nosepiece and mouthpiece units 105, 109. As will bedescribed in more detail hereinbelow, the delivery device is a re-usabledevice, to which containers C, in this embodiment capsules, containingsubstance to be delivered to the nasal cavity of a subject are removablyloaded.

As illustrated in FIGS. 12 and 13, the containers C comprise first andsecond body parts 115, 117, which together define an enclosed chamber119 and are movably disposed, here slideably disposed relative to oneanother. The body parts 115, 117 each include at least one aperture 121,123, in this embodiment a plurality of apertures 121, 123, which areclosed with the body parts 115, 117 in a first, closed configuration andare opened by sliding of the body parts 115, 117 to a second, openconfiguration in which the apertures 121, 123 in the body parts 115, 117are aligned.

In this embodiment the body parts 115, 117 include inter-engaging guides125, 127, which provide for axial sliding of the body parts 115, 117without any rotation thereof, thereby ensuring alignment of theapertures 121, 123.

In this embodiment the housing 103 comprises a body 135 to which thenosepiece unit 105, the mouthpiece unit 109 and the substance-supplyunit 111 are disposed, and a cover 137, here a hinged lid, which isoperable between a closed position in which the nosepiece and mouthpieceunits 105, 109 are enclosed and an open position in which the nosepieceand mouthpiece units 105, 109 are exposed for use.

The body 135 includes a container aperture 139, in this embodiment anelongate aperture, through which a container C is loaded and removedfrom the substance-supply unit 111, as will be described in more detailhereinbelow.

The nosepiece unit 105 comprises a nosepiece 141, in this embodiment afrusto-conical section, which is inserted into a nostril of the subject,here to provide a sealing fit therewith, and a flow channel 143 which isfluidly connected to the nosepiece 141 and includes a grid 145, in thisembodiment a gauze, at one, lower end thereof.

The mouthpiece unit 109 comprises a mouthpiece 147 which in use isgripped in the lips of a subject, and a one-way, non-return valve 149which is fluidly connected to the mouthpiece 147 and is operative toprevent inhalation by the subject through the mouthpiece 147.

The substance-supply unit 111 comprises a support member 151 which isfixed to the body 135 of the housing 103, and a body section 153 whichis movably disposed, in this embodiment rotatably disposed, to thesupport member 151.

The support member 151 includes a cam member 161 which includes a camtrack 163 which extends between first and second positions 165, 167 andincludes stops 169 at the respective ends thereof, in this embodiment atangular positions of 180 degrees. In this embodiment the cam track 163includes a first cam section, corresponding to a first phase ofrotation, which is inclined from a first, lower position 165 to thesecond, higher position 167 and a second cam section, corresponding to asecond phase of rotation, which is inclined from the second, higherposition 167 to the first, lower position 165.

The body section 153 comprises a body member 171, in this embodiment atubular member, which defines a container chamber 172 and includes afirst, container-receiving aperture 173 in the lateral wall thereof forreceiving a container C, a second, inlet flow aperture 175 at one, thelower, end thereof, and a third, outlet flow aperture 177 at the other,upper, end thereof which receives the flow channel 143 of the nosepieceunit 105 and is slideably disposed thereto. As will be described in moredetail hereinbelow, the body section 153 is rotatable between a first,closed position in which the container-receiving aperture 173 is closedby the enclosure member of the body 135 and the inlet aperture 175 is influid communication with the mouthpiece unit 109, and a second, openposition in which the container-receiving aperture 173 is open to thecontainer aperture 139 in the body 135 and the inlet aperture 175 isclosed.

The body section 153 further comprises a grid 181, here a gauze, whichis located within the body member 171 at a location intermediate thecontainer-receiving aperture 173 and the inlet flow aperture 175, whichacts to support a container C when loaded into the body member 171. Aswill be described in more detail hereinbelow, the grid 181 is configuredto compress the container C against the grid 145 in the nosepiece unit105, such as to open the container C by aligning the apertures 121, 123thereof.

The body section 153 further comprises a cam follower 179, in thisembodiment in the form of a projection which projects laterally from thebody member 171, which is configured to ride on the cam track 163 of thecam member 161 and provide for axial displacement of the body section153 relative to the support member 151 on rotation of the body section153.

In this embodiment the body section 153 is rotatable between a closedposition, as illustrated in FIGS. 7 to 9, in which the cam follower 179is located on the cam track 163 of the cam member 161 at the first,lower position 165, through an intermediate position, as illustrated inFIG. 11, in which the cam follower 179 is located on the cam track 163of the cam member 161 at the second, raised height 167, and to an openposition, as illustrated in FIG. 10, in which the cam follower 179 islocated on the cam track 163 of the cam member 161 at the first height165. When the cam follower 179 is located on the cam track 163 of thecam member 161 at the first height 165, the grid 181 of the body section153 is spaced from the grid 145 of the nosepiece unit 105, such as toallow for axial movement and rotation of a contained container C, and,when the cam follower 179 is located on the cam track 163 of the cammember 161 at the second height 167, the grid 181 of the body section153 is spaced more closely to the grid 145 of the nosepiece unit 105,such as to cause the compression of the body parts 115, 117 of thecontainer C and thereby open the container C.

The body section 153 further comprises an actuating member 183, in thisembodiment in the form of a knob, which can be gripped by the subjectand is connected to the body member 171, in this embodiment at a lowerend thereof, such as to provide for rotation of the body member 171.

In one embodiment the mouthpiece unit 109 could include a heat exchangerwhich is in fluid communication with the mouthpiece 147 and acts to drawheat from the exhaled air flow as delivered through the mouthpiece 147,thus decreasing the temperature of the delivered air flow. By decreasingthe temperature of the air flow, the humidity of the air flow isreduced, with the water vapor condensing in the heat exchanger, and theimpact of condensation is significantly reduced, thus allowing forsuccessive doses of powdered substance to be delivered without affectingthe release of powdered substance from the containers C.

In this embodiment the container chamber 172 and the grids 145, 181, ascomponents which contact the container C and the contained powder, arefabricated from a material having a low moisture sensitivity, here aplastics material, such as to reduce any tendency to become tacky in thepresence of moisture, and therefore reduce the tendency for thecontainer C and the powdered substance as contained thereby to adhere tothe wall of the container chamber 172 or the grids 145, 181.

In this embodiment the nosepiece 141, as a component which contacts thepowdered substance, is fabricated from a material having a low moisturesensitivity, here a plastics material, such as to reduce any tendency tobecome tacky in the presence of moisture, and therefore reduce thetendency for the powdered substance to adhere to the wall of thenosepiece 141.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from amaterial which has a reduced tendency to become tacky in the presence ofmoisture, as occurs with gelatine capsules, and therefore reduce thetendency for the container C to adhere to the wall of the containerchamber 172 or the grids 145, 181.

In one embodiment the container C is formed of a cellulose derivative,such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose,methylcellulose, ethylcellulose and carboxymethylcellulose

In another embodiment the container C can comprise a plastics material,preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweightmaterial, such as thin-wall section polymeric materials, which reducesthe energy required to move the container C, typically by one or both ofvibration and rotation, and thereby allow the delivery device to beoperated at reduced flow rates, which is particularly advantageous fornasal delivery.

In an alternative embodiment the container C can include an outercoating of a material, such as parylene, which has a reduced tendency tobecome tacky in the presence of moisture, as occurs with gelatinecapsules, and therefore reduce the tendency for the container C toadhere to the wall of the container chamber 172 or the grids 145, 181.

In this embodiment, the container C is cylindrical in shape withhemispherical ends.

In other embodiments the container C could have other geometric forms,such as spherical, which allows for efficient powder release at low flowrates.

Operation of the delivery device will now be described hereinbelow.

A subject first operates the actuating member 183 such as to rotate thebody section 153 from the closed position, as illustrated in FIGS. 7 to9, in this embodiment through 180 degrees, to the open position, asillustrated in FIG. 10, in which the container aperture 173 in the bodymember 171 is aligned with the container aperture 139 in the housing103, such as to allow a container C to be loaded into the containerchamber 172 of the body member 171.

The subject then again operates the actuating member 183 such as toreturn the body section 153 to the closed position. In so operating theactuating member 183, the body section 153 is first moved from the openposition in which the cam follower 179 on the body section 153 islocated on the cam track 163 of the cam member 161 at the first, lowerheight 165, through an intermediate position, as illustrated in FIG. 11,in which the cam follower 179 is located on the cam track 163 of the cammember 161 at the second, raised height 167. In this intermediateposition, the grid 181 of the body section 153 is spaced more closely tothe grid 145 of the nosepiece unit 105, such as to cause the compressionof the body parts 115, 117 of the container C and thereby open thecontainer C. With continued operation of the actuating member 183, thebody section 153 is moved from the intermediate position to the closedposition, as illustrated in FIGS. 7 to 9, in which the cam follower 179is located on the cam track 163 of the cam member 161 at the first,lower height 165 and the grid 181 of the body section 153 is spacedfurther apart from the grid 145 of the nosepiece unit 105, such as toallow for axial movement and rotation of a contained container C, thecontainer aperture 173 in the body member 171 is closed by the enclosuremember of the housing 103 and the inlet aperture 175 is in fluidcommunication with the mouthpiece unit 109.

The subject then inserts the nosepiece 141 into one of his/her nostrils,grips the mouthpiece 147 in his/her mouth, and exhales through themouthpiece 147.

The exhaled air flow, where having a sufficient flow rate, is thendriven through the container chamber 172 of the body member 171 of thebody section 153, which acts to move the container C, in this embodimentby vibration and rotation, and entrain the powdered substance ascontained by the container C.

The exhaled air flow, as then entraining the powdered substance, isdelivered though the nosepiece 141 into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to passaround the posterior region of the nasal septum, and into the othernasal cavity, thereby achieving a bi-directional air flow as describedin the applicants' earlier WO-A-00/051672.

Following use of the device, the actuating member 183 is first operatedsuch as to rotate the body section 153 from the closed position, in thisembodiment through 180 degrees, to the open position, in which thecontainer aperture 173 in the body member 171 is aligned with thecontainer aperture 139 in the housing 103, such as to allow the usedcontainer C to be removed from the container chamber 172 of the bodymember 171, and the actuating member 183 is subsequently operated suchas to rotate the body section 153 from the open position, in thisembodiment through 180 degrees, to the closed position, in which thecontainer aperture 173 in the body member 171 is closed.

FIGS. 14 to 17 illustrate a delivery device in accordance with a thirdembodiment of the present invention.

The delivery device comprises a housing 203, a nosepiece unit 205, amouthpiece unit 209 and a substance-supply unit 211 which is fluidlyconnected to the nosepiece and mouthpiece units 205, 209. As will bedescribed in more detail hereinbelow, the delivery device is a re-usabledevice, to which containers C, in this embodiment capsules, containingsubstance to be delivered to the nasal cavity of a subject are removablyloaded.

As illustrated in FIGS. 14 and 15, the containers C comprise a main bodypart 215, in this embodiment of cylindrical section, and first andsecond supports 217 at the respective ends of the body part 215, whichact as bearings about which the container C is rotated. In thisembodiment the supports 217 comprise hemi-spherical structures, whichare of smaller radial dimension than the body part 215 and located onthe longitudinal axis of the body part 215. In one embodiment thesupports 217 could be offset relative to one another or eccentricallyweighted, such as to promote the vibration of the container C onrotation.

In this embodiment the housing 203 comprises a body 235 to which thenosepiece unit 205, the mouthpiece unit 209 and the substance-supplyunit 211 are disposed.

The body 235 includes a container aperture 239, through which acontainer C is loaded and removed from the substance-supply unit 211, aswill be described in more detail hereinbelow.

The nosepiece unit 205 comprises a nosepiece 241, in this embodiment asdefined by a tubular section, which is inserted into a nostril of thesubject, here to provide a sealing fit therewith.

In one embodiment the nosepiece unit 205 can include a grid, such as agauze, for preventing the container C or parts thereof from passingthrough the nosepiece 241 and into the nasal cavity of the subject.

The mouthpiece unit 209 comprises a mouthpiece 247 which in use isgripped in the lips of a subject, and a heat exchanger 249 which is influid communication with the mouthpiece 247 and acts to draw heat fromthe exhaled air flow as delivered through the mouthpiece 247, thusdecreasing the temperature of the delivered air flow. By decreasing thetemperature of the air flow, the humidity of the air flow is reduced,with the water vapor condensing in the heat exchanger 249, and theimpact of condensation is significantly reduced, thus allowing forsuccessive doses of powdered substance to be delivered without affectingthe release of powdered substance from the containers C.

In this embodiment the heat exchanger comprises a plurality of parallel,elongate tubes.

The substance-supply unit 211 comprises a container-receiving member251, which is slideably disposed within the container aperture 239 inthe housing 203 between an open position for enabling the loading of acontainer C thereinto, as illustrated in FIGS. 14 and 15, and a closedposition, as illustrated in FIGS. 16 and 17, in which the container C iscontained within the housing 203.

In this embodiment the container-receiving member 251 comprises a cavity253 which defines an air flow channel from the mouthpiece 245 to thenosepiece 241 and includes first and second supports 255, in thisembodiment part-spherical structures which act as bearings and areconfigured to receive the respective supports 217 of the container C,such that, on delivery of an exhalation air flow through the cavity 253,the container C is rotated by the supports 217 thereof.

The substance-supply unit 211 further comprises a locking mechanism 261which is operative to lock the substance-supply unit 211 in the closedposition.

In this embodiment the locking mechanism 261 comprises at least one armmember 263, in this embodiment a plurality of arm members 263 a, 263 b,which are deflectable, here inwardly, and each include a detent 265which is engageable with a surface of the housing 203, such as to lockthe substance-supply unit 211 in the closed position. In this embodimentthe substance-supply unit 211 is located in the locked position bypushing the substance-supply unit 211 into the housing 203, which causesthe detents 265 on the arm members 263 a, 263 b to ride over the housing203 and be locked behind a surface thereof, and withdrawn from thehousing 203 by deflecting the arm members 263 a, 263 b, here bysqueezing the arm members 263 a, 263 b inwardly, such as to release thedetents 265 from engagement with the respective surfaces of the housing203, and pulling the substance-supply unit 211 outwardly.

The substance-supply unit 211 further comprises a rupturing mechanism271 which is operable to rupture the container C as contained by thenosepiece unit 205.

In this embodiment the rupturing mechanism 271 comprises an actuatingmember 273, here in the form of a button, which is configured to bedepressed by the subject, as illustrated in FIG. 17, a piercing element275, here including two pins, which is supported by the actuating member273 and operable to drive the piercing element 275 to pierce thecontainer C, and thereby provide for release of the contained powderedsubstance on the generation of a flow through the cavity 253 in thecontainer-receiving member 251, and a resilient element 277, here acompression spring, for returning the actuating member 273 to the restposition following piercing of the container C.

In this embodiment the container-receiving member 251 and the grid, ascomponents which contact the container C and the contained powder, arefabricated from a material having a low moisture sensitivity, here aplastics material, such as to reduce any tendency to become tacky in thepresence of moisture, and therefore reduce the tendency for thecontainer C and the powdered substance as contained thereby to adhere tothe container-receiving member 251 or the grid.

In this embodiment the nosepiece 241, as a component which contacts thepowdered substance, is fabricated from a material having a low moisturesensitivity, here a plastics material, such as to reduce any tendency tobecome tacky in the presence of moisture, and therefore reduce thetendency for the powdered substance to adhere to the wall of thenosepiece 241.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from amaterial which has a reduced tendency to become tacky in the presence ofmoisture, as occurs with gelatine capsules, and therefore reduce thetendency for the container C to adhere to the container-receiving member251 or the grid.

In one embodiment the container C is formed of a cellulose derivative,such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose,methylcellulose, ethylcellulose and carboxymethylcellulose

In another embodiment the container C can comprise a plastics material,preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweightmaterial, such as thin-wall section polymeric materials, which reducesthe energy required to move the container C, typically by one or both ofvibration and rotation, and thereby allow the delivery device to beoperated at reduced flow rates, which is particularly advantageous fornasal delivery.

In an alternative embodiment the container C can include an outercoating of a material, such as parylene, which has a reduced tendency tobecome tacky in the presence of moisture, as occurs with gelatinecapsules, and therefore reduce the tendency for the container C toadhere to the container-receiving member 251 or the grid.

Operation of the delivery device will now be described hereinbelow.

A subject first withdraws the substance-supply unit 211 by deflectingthe arm members 263 a, 263 b of the locking mechanism 261, here bysqueezing the arm members 263 a, 263 b inwardly, such as to release thedetents 265 thereof from engagement with the respective surfaces of thehousing 203, and pulling the substance-supply unit 211 outwardly.

The subject then loads a container C into the cavity 253 in thecontainer-receiving member 251, such that the end parts 217 of thecontainer C are located on the respective supports 255 of the cavity253. It will be appreciated that this design allows the containers C fordifferent substances to be sized differently, such as to prevent thedevice from being used improperly with different substances.

The subject then closes the substance-supply unit 211 by pushing thesubstance-supply unit 211 into the housing 203, which causes the detents265 on the arm members 263 a, 263 b to ride over the housing 203 and belocked behind a surface thereof.

The subject then operates the rupturing mechanism 271 to rupture thecontainer C, in this embodiment by depressing the actuating member 273thereof, as illustrated in FIG. 17, following which the actuating member273 is returned to the rest position by the biasing element 277 thereof.

The subject then inserts the nosepiece 241 into one of his/her nostrils,grips the mouthpiece 247 in his/her mouth, and exhales through themouthpiece 247.

The exhaled air flow, where having a sufficient flow rate, is thendriven through the cavity 253 of the container-receiving member 251,which acts to move the container C, in this embodiment by vibration androtation, and entrain the powdered substance as contained by thecontainer C.

The exhaled air flow, as then entraining the powdered substance, isdelivered though the nosepiece 241 into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to passaround the posterior region of the nasal septum, and into the othernasal cavity, thereby achieving a bi-directional air flow as describedin the applicants' earlier WO-A-00/051672.

Following use of the device, the substance-supply unit 211 is opened bydeflecting the arm members 263 a, 263 b of the locking mechanism 261,here by squeezing the arm members 263 a, 263 b inwardly, such as torelease the detents 265 thereof from engagement with the respectivesurfaces of the housing 203, and pulling the substance-supply unit 211outwardly.

The subject then unloads the container C from the cavity 253 in thecontainer-receiving member 251, and closes the substance-supply unit211, in this embodiment by pushing the substance-supply unit 211 intothe housing 203, which causes the detents 265 on the arm members 263 a,263 b to ride over the housing 203 and be locked behind respectivesurfaces thereof.

FIGS. 18 to 26 illustrate a delivery device in accordance with a fourthembodiment of the present invention.

The delivery device comprises a main, body assembly 303 and a nosepieceunit 305, which contains a container C, in this embodiment a capsule,containing substance to be delivered to the nasal cavity of a subjectand is removably fitted to the body assembly 303, such as to allow forthe re-use of the device, as will be described in more detailhereinbelow.

The body assembly 303 comprises a housing 307, a mouthpiece unit 309, arupturing mechanism 315 which is operable to rupture the container C ascontained by the nosepiece unit 305, and a locking mechanism 317 forpreventing operation of the rupturing mechanism 315 without a nosepieceunit 305 being fitted to the housing 307 and also after a predeterminednumber of operations.

The housing 307 comprises a body 319 which defines a cavity 321 andincludes a first, fitting aperture 323 in which the nosepiece unit 305is fitted and a second, clearance aperture 325 through which extends anactuating member 371 of the rupturing mechanism 315.

In this embodiment the body 319 includes at least one, here a pluralityof projections 327 which are disposed about the fitting aperture 323,such as to provide for the screw-fitting of the nosepiece unit 305 tothe housing 307.

The mouthpiece unit 309 comprises a mouthpiece 331 which in use isgripped in the lips of a subject, an air flow channel 333 which isfluidly connected to the cavity 321 of the housing 307, and a one-way,non-return valve 335 for preventing inhalation through the mouthpiece331.

In this embodiment the housing 307 and the mouthpiece unit 309 areintegrally formed, typically from a plastics material.

The nosepiece unit 305 comprises a body member 341 which is configuredto fit in the fitting aperture 323 in the housing 307, a nosepiece 343,here as defined by a tubular section, which is supported by the bodymember 341 and is in use inserted into a nostril of the subject, here toprovide a sealing fit therewith, and a container chamber 345 which is influid communication with the nosepiece 343 and contains a container Ccontaining a powdered substance for delivery to the nasal cavity of thesubject.

In this embodiment the body member 341 includes at least one, here aplurality of recesses 351 which are disposed thereabout incorrespondence to the projections 327 which are disposed about thefitting aperture 323 of the housing 307, such as to provide for thescrew-fitting of the nosepiece unit 305 to the housing 307. With thisconfiguration, fitting of the nosepiece unit 305 to the housing 307first requires insertion of the nosepiece unit 305 into the housing 307and subsequently rotation of the nosepiece unit 305 in one sense, herein a counter-clockwise sense when viewed from above.

The nosepiece unit 305 further comprises a release member 355 which isconfigured to engage a counterpart latch member 377 on the actuatingmember 371 of the rupturing mechanism 315, such as to release theactuating member 371 to an operative position following fitting of thenosepiece unit 305, as will be described in more detail hereinbelow.

In this embodiment the release member 355 comprises a radially-directedarm, which comprises a support element 359 which is attached to thecontainer chamber 345, an engagement element 361 which is operative toengage the latch member 377 of the actuating member 371 of the rupturingmechanism 315, and a frangible connection element 363, here a flexible,deformable element, which connects the support element 359 to theengagement element 361 in such a manner that the engagement element 361presents a rigid structure when rotated in the one, fitting sense infitting the nosepiece unit 305 to the housing 307 and is deformed, hereplastically deformed, when rotated in the other, removal sense inremoving the nosepiece unit 305 from the housing 307, as represented inFIGS. 20 and 21. In this embodiment the connection element 363 is bent,and permanently deformed, by engagement with the latch member 377 of theactuating member 371 of the rupturing mechanism 315 on removing thenosepiece unit 305 from the housing 307, and this deformation preventsre-use of the nosepiece unit 305, insofar as the release member 355 isno longer operative to release the actuating member 371 of the rupturingmechanism 315 to a release position. With this configuration, thepossibility of using a used nosepiece unit 305 is avoided and thesubject is thus ensured of receiving a dose of substance with eachoperation of the device.

In this embodiment the nosepiece unit 305 further comprises a grid 363,here a gauze, which is disposed between the nosepiece 341 and thecontainer chamber 345, such as to prevent the container C or any partsthereof, such as resulting from rupturing of the container C, frompassing through the nosepiece 341 and entering the nasal cavity of thesubject.

In this embodiment the container chamber 345 and the grid 363, ascomponents which contact the container C and the contained powder, arefabricated from a material having a low moisture sensitivity, here aplastics material, such as to reduce any tendency to become tacky in thepresence of moisture, and therefore reduce the tendency for thecontainer C and the powdered substance as contained thereby to adhere tothe wall of the container chamber 345 or the grid 363.

In this embodiment the nosepiece 341, as a component which contacts thepowdered substance, is fabricated from a material having a low moisturesensitivity, here a plastics material, such as to reduce any tendency tobecome tacky in the presence of moisture, and therefore reduce thetendency for the powdered substance to adhere to the wall of thenosepiece 341.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from amaterial which has a reduced tendency to become tacky in the presence ofmoisture, as occurs with gelatine capsules, and therefore reduce thetendency for the container C to adhere to the wall of the containerchamber 345 or the grid 363.

In one embodiment the container C is formed of a cellulose derivative,such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose,methylcellulose, ethylcellulose and carboxymethylcellulose

In another embodiment the container C can comprise a plastics material,preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweightmaterial, such as thin-wall section polymeric materials, which reducesthe energy required to move the container C, typically by one or both ofvibration and rotation, and thereby allow the delivery device to beoperated at reduced flow rates, which is particularly advantageous fornasal delivery.

In an alternative embodiment the container C can include an outercoating of a material, such as parylene, which has a reduced tendency tobecome tacky in the presence of moisture, as occurs with gelatinecapsules, and therefore reduce the tendency for the container C toadhere to the wall of the container chamber 345 or the grid 363.

In this embodiment, the container C is cylindrical in shape withhemispherical ends.

In other embodiments the container C could have other geometric forms,such as spherical, which allows for efficient powder release at low flowrates.

In this embodiment the rupturing mechanism 315 comprises an actuatingmember 371, here in the form of a button, which extends through theclearance aperture 325 in the housing 307 and is configured to bedepressed by the subject, a piercing element 375, here including twopins, which is supported by the actuating member 371 and operable todrive the piercing element 375 to pierce the container C, and therebyprovide for release of the contained powdered substance on thegeneration of a flow through the container chamber 345 of the nosepieceunit 305, and a biasing element 376, here a compression spring, fornormally biasing the actuating member 371 outwardly of the housing 307,such as to withdraw the piercing element 375.

The actuating member 371 includes a latch member 377 which is operativeto lock the actuating member 371 in an intermediate position, asillustrated in FIG. 26, in which the piercing elements 375 are withdrawnfrom the container chamber 345, such as to allow for rotation of thecontained container C, and first and second lug members 379, 381 whichare operative to operate the locking mechanism 317 and prevent furtherdepression of the actuating member 371 from the intermediate position.

In this embodiment the latch member 377 comprises a resilient arm 383and a detent 385 at one end of the arm 383, which engages a surface ofthe housing 307 to latch the actuating member 371 in the intermediateposition. In this embodiment the latch member 377 is released, here bydeflection of the resilient arm 383, by engagement with the releasemember 355 of the nosepiece unit 305 in fitting the nosepiece unit 305to the housing 307. As described hereinabove, the release member 355 ofthe nosepiece unit 305 is not operative to release the latch member 377on removal of the nosepiece unit 305 from the housing 307, as therelease member 355 is deformed through engagement with the latch member377.

In this embodiment the locking mechanism 317 comprises a rotatablemember 391 which includes a plurality of first engagement elements 393,in this embodiment disposed on a first annulus centred about therotation axis of the rotatable member 391, and a plurality of secondengagement elements 395 which are disposed on a second, larger annuluscentred about the rotation axis of the rotatable member 391.

The first engagement elements 393 each include an outwardly-facing,locking surface 397 which, when the actuating member 371 of therupturing mechanism 315 is in the intermediate position, acts to engagean adjacent first lug 379 of the actuating member 371, such as toprevent depression of the same.

The second engagement elements 395 each include an indexing surface 399which is engaged by respective ones of the lugs 379, 381 such as toindex the rotatable member 351, such that the actuating member 371 ofthe rupturing mechanism 315 can be depressed to rupture the containedcontainer C following release of the actuating member 371 to thereleased position and prevent further depression of the actuating member371 following release of the actuating member 371 to the intermediateposition.

In one embodiment the mouthpiece unit 309 could include a heat exchangerwhich is in fluid communication with the mouthpiece 331 and acts to drawheat from the exhaled air flow as delivered through the mouthpiece 331,thus decreasing the temperature of the air flow as delivered to anddownstream of the container member 345. By decreasing the temperature ofthe air flow, the humidity of the air flow is reduced, with the watervapor condensing in the heat exchanger, and the impact of condensationis significantly reduced, thus allowing for successive doses of powderedsubstance to be delivered without affecting the release of powderedsubstance from the containers C.

Operation of the delivery device will now be described hereinbelow.

A subject first takes a nosepiece unit 305 for fitting to the bodyassembly 303, as illustrated in FIG. 22.

The subject then inserts a nosepiece unit 305 into the fitting aperture323 in the housing 307, as illustrated in FIG. 23.

The subject then rotates the nosepiece unit 305, in this embodiment inthe counter-clockwise sense from above, such as to lock the nosepieceunit 305 to the housing 307, as illustrated in FIG. 24. This rotation ofthe nosepiece unit 305 causes the release member 355 thereof to engagethe latch element 377 of the actuating member 371, such as to releasethe same, here by deflection of the resilient arm 383 of the latchelement 377 through engagement with the release member 355.

The subject then operates the rupturing mechanism 315 to rupture thecontained container C, as illustrated in FIG. 25, following which thesubject releases the actuating member 371, which returns to theintermediate position, as illustrated in FIG. 26.

The subject then inserts the nosepiece 341 into one of his/her nostrils,grips the mouthpiece 331 in his/her mouth, and exhales through themouthpiece 331.

The exhaled air flow, where having a sufficient flow rate, is thendriven through the cavity 321 in the housing 307 and the containerchamber 345, which acts to move the container C, in this embodiment byvibration and rotation, and entrain the powdered substance as containedby the container C.

The exhaled air flow, as then entraining the powdered substance, isdelivered though the nosepiece 341 into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to passaround the posterior region of the nasal septum, and into the othernasal cavity, thereby achieving a bi-directional air flow as describedin the applicants' earlier WO-A-00/051672.

Following use of the device, the nosepiece unit 305 is then removed fromthe device assembly 303, in order to allow for the device to be re-used.

The nosepiece unit 305 is removed by rotating the nosepiece unit 305relative to the housing 307, in this embodiment in a clockwise sensewhen viewed from above, and withdrawing the nosepiece unit 305 from thefitting aperture 323 in the housing 307.

On rotating the nosepiece unit 305, the release arm 355 of the nosepieceunit 305 engages the latch member 377 of the actuating member 371, inthis embodiment through engagement with the engagement element 361 ofthe release member 355, which causes the connection element 363 of therelease member 355 to be bent, and permanently deformed. As describedhereinabove, this deformation prevents re-use of the nosepiece unit 305,insofar as the release member 355 is no longer operative to release theactuating member 371 of the rupturing mechanism 315 to the operativeposition.

Finally, it will be understood that the present invention has beendescribed in its preferred embodiments and can be modified in manydifferent ways without departing from the scope of the invention asdefined by the appended claims.

In one embodiment the powdered substance can also be formulated, forexample, by coating or blending, such as to reduce the hygroscopicityand transiently increase the dissolution time, and thus reduce any lossof powdered substance in the device due to interaction with condensationon the internal surfaces of the device.

Also, the delivery devices of the described embodiments have beendescribed particularly in relation to the use of capsules. It is to beunderstood that the present invention has application with any kind ofpowder delivery system, including blisters, and can be configured as asingle-use or multi-use device.

1. A nasal delivery device for delivering particulate substance to thenasal airway of a subject, the delivery device comprising: a bodyassembly including a mouthpiece unit which includes a mouthpiece throughwhich the subject in use exhales, and a substance-supply unit which isfluidly connected to the mouthpiece unit and configured to receive areplaceable nosepiece unit which includes a nosepiece and contains acontainer containing particulate substance, wherein the substance-supplyunit is actuatable to provide particulate substance for delivery to thenasal airway of the subject. 2-9. (canceled)
 10. A nasal delivery devicefor delivering particulate substance to the nasal airway of a subject,the delivery device comprising: a mouthpiece unit which includes amouthpiece through which the subject in use exhales; a nosepiece unitwhich includes a nosepiece for fitting to a nostril of the subject; anda substance-supply unit which is configured to receive a containercontaining particulate substance and operable to provide a meteredamount of substance in fluid communication with the mouthpiece andnosepiece units, such that an exhalation air flow delivered through thesubstance-supply unit entrains the substance. 11-24. (canceled)
 25. Anasal delivery device for delivering particulate substance to the nasalairway of a subject, the delivery device comprising: a body assemblyincluding a mouthpiece unit which includes a mouthpiece through whichthe subject in use exhales, and a substance-supply unit which is fluidlyconnected to the mouthpiece unit and actuatable to provide particulatesubstance for delivery to the nasal airway of the subject; wherein thebody assembly is configured to receive a replaceable nosepiece unitwhich includes a nosepiece and contains a container containingparticulate substance. 26-47. (canceled)